Associations of aspirin, statins, and metformin with lung cancer risk and related mortality: time-dependent analysis of population-based nationally representative data.

OBJECTIVES The aim of this study was to investigate the associations of aspirin, metformin, and statins with lung cancer risk and mortality using population-based nationwide cohort data. METHODS This study included a total of 732,199 participants who had undergone a national health check-up in 2002-2003. Lung cancer incidence and mortality were identified using a registered lung cancer diagnosis code (ICD-10 code C34) and the Korean National Death Registry. The study participants were followed from January 1, 2004 to 31 December 2013. Medication exposure was defined by cumulative duration of use and cumulative defined daily dose (cDDD) per 2-year interval. To avoid immortal time bias, drug exposure was inserted as a time-dependent variable in Cox analysis, which evaluated the associations of these medications with lung cancer. RESULTS Metformin use had protective association with lung cancer incidence (P's-for-trend = 0.008) and mortality (P's-for-trend <0.001) in a dose-response fashion, and these associations were prominent among participants with cDDD of metformin ≥ 547.5, compared with non-diabetic patients. Lung cancer mortality was dose-dependently reduced with the use of aspirin ([P's-for-trends 0.046] and statin [P's-for-trends <0.001]). Combined use of aspirin, statins and metformin showed more prominent protective associations with lung cancer risk and mortality. CONCLUSION Use of aspirin, metformin, and statins had independent protective associations with lung cancer mortality, and metformin had inverse association with lung cancer risk. Further studies are necessary to develop clinically applicable anticancer strategies of these drugs for the reduction of lung cancer and related mortality.